Over the past two decades, we have arrived at a deeper scientific understanding of fragile X syndrome (FXS); concurrently, our awareness ofthe intrinsic complexity of pathogenic mechanisms contributing to brain dysfunction has grown. New discoveries from fine-grained, developmental analyses of novel animal models and humans with FXS are essential for achieving needed breakthroughs, so that we can eventually design interventions that produce significant, long-term benefits for affected individuals. Accordingly, investigators comprising the Collaborative Fragile X Center at Stanford seek to fundamentally and substantively advance knowledge ofthe pathophysiology of FXS at multiple levels of scientific inquiry (molecular, gene, synapse, brain circuits/systems, behavior), in novel animal models and affected humans, and from the perspective of the developmental dynamics of brain maturation. We further seek to provide vital new information about how targeted environmental, pharmacologic and behavioral approaches can positively affect function of the FXS brain. To accomplish these objectives, 4 specific aims will be addressed: Aim 1 (Science): To engage a highly collaborative, trans-disciplinary team of investigators who will address focused and challenging questions concerning FXS pathophysiology through three interactive, interdependent and synergistic projects that emphasize innovative cross-species experiments and comparisons (novel mouse models and humans with FXS). Collectively, these projects take multi-level, state-of-the-art scientific approaches, spanning molecules, receptors, synapses, circuits and behavioral phenotypes, and assessing response to targeted environmental, pharmacological and behavioral probes. This research will yield information that represents substantive and translation-relevant advances in our understanding of FXS pathogenesis. Aim 2 (Management): To maintain an efficient administrative structure and effective scientific oversight through the establishment of an Administrative Core that promotes coordination, communication and collaboration, provides financial oversight, expert bio statistical consultation and database management, facilitates recruitment of human research participants, and interacts with the Center Administrative and Advisory Committees. Aim 3 (Investigators): To directly and substantively involve early-stage investigators and investigators whose primary field of expertise is outside of FXS in Center scientific activities. Aim 4 (Training and Education): To establish and manage selected educational and training opportunities including a summer undergraduate program, monthly FXS journal club and participation in an annual symposium.